Transparent hydrogel and method of making the same from functionalized natural polymers

Abstract

The present disclosure relates to a hydrogel derived from a methacrylated or acrylated natural polymer and a synthetic polymer, and a method of preparing the same. The disclosure further relates to 3D scaffolds and implants comprising said hydrogel.

The invention claimed is: 
     
       1. A hydrogel of a cross-linked polymer network comprising:
 at least one first polymer including a collagen mimetic peptide (CMP) having amine groups, the CMP including methacrylate or acrylate functional groups along its triple helical chain and connected to a template polymer having at least two arms; and 
 at least one second polymer including a synthetic polymer or a natural polymer having at least two functional groups selected from thiol, acrylate and methacrylate, 
 wherein the first and the second polymers are intermolecularly cross-linked via said functional groups, 
 wherein the hydrogel has a light transmission of at least 80% of light in a range of 400-700 nm, and 
 wherein a total concentration of polymers in the hydrogel is at least 2 weight %. 
 
     
     
       2. The hydrogel according to  claim 1 , wherein the template polymer is selected from multiarm polyvinyl chloride, spider silk, succinylated poly(N-isoacrylamide), or a terpolymer of poly(N-isopropylacrylamide-coacrylic acid-coacryloxysuccinimide (PNiPAAm-coAAc-coASI). 
     
     
       3. The hydrogel according to  claim 1 , wherein the second polymer is a polymer selected from functionalized polyethylene glycol (PEG), polyvinyl alcohol (PVA), polyethylene glycol-diacrylate (PEGDA), PEG methacrylate (PEGMA), poly(hydroxyethyl methacrylate) (pHEMA), polyethylene glycol methyl ether methacrylate (PEGMEM), poly(pentaerythritol triacrylate) or poly(N-isopropylacryl amide) (PNIPAAm). 
     
     
       4. The hydrogel according to  claim 1 , wherein the second polymer has three or more arms. 
     
     
       5. The hydrogel according to  claim 1 , wherein the hydrogel is cross-linked photochemically or via Michael addition reaction with 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-Hydroxysuccinimide (NHS). 
     
     
       6. The hydrogel according to  claim 1 , wherein the light transmission is at least 90%. 
     
     
       7. A three dimensional scaffold comprising cells and the hydrogel according to  claim 1 . 
     
     
       8. The scaffold according to  claim 7 , wherein the cells are stem cells. 
     
     
       9. An implant comprising the hydrogel according to  claim 1 . 
     
     
       10. The implant according to  claim 9 , wherein the implant is a cornea implant. 
     
     
       11. A method comprising:
 replacing a damaged or malfunctioning cornea with the implant according to  claim 10 . 
 
     
     
       12. A method of preparing the hydrogel according to  claim 1 , the method comprising:
 providing a first aqueous solution of a first polymer including a collagen mimetic peptide (CMP) having amine groups, the CMP including methacrylate or acrylate functional groups and connected to a template polymer having at least two arms; 
 providing a second aqueous solution of a second polymer including a synthetic polymer having at least two functional groups selected from thiol, acrylate and methacrylate, or synthetic monomers having thiol, acrylate and/or methacrylate functional groups; 
 mixing the first polymer and the second polymer or synthetic monomers to cross-link the functional groups of the first polymer and the second polymer or synthetic monomers and obtain a mixture having a total polymer concentration of at least 2 weight %; and 
 applying UV radiation to the mixture. 
 
     
     
       13. The method according to  claim 12 , wherein
 the first polymer is methacrylated CMP, and 
 a pH of the first aqueous solution is less than 5 or more than 10. 
 
     
     
       14. The method according to  claim 12 , wherein a total concentration of polymers in the mixture is at least 12 weight %. 
     
     
       15. The method according to  claim 12 , wherein the mixing is performed using a syringe mixing system. 
     
     
       16. A method of using the hydrogel according to  claim 1  in at least one of lab-on-a-chip systems, microscopy and microarray substrates, cell and tissue culture dishes, microwell plates, microfluidic or sampling, separation, purification, and analytical tools, wherein the hydrogel is configured to support cell growth, proliferation, differentiation, and tissue formation. 
     
     
       17. An injectable composition comprising:
 a first aqueous solution including collagen mimetic peptide (CMP) having amine groups, the CMP including methacrylate or acrylate functional groups along its triple helical chain and connected to a template polymer having at least two arms; and 
 a second aqueous solution including a synthetic polymer having two or more functional groups selected from thiol, acrylate and/or methacrylate, 
 wherein a polymer concentration in each of the first and second aqueous solutions is not more than 3 weight %, 
 wherein the first and second aqueous solutions form a gel when mixed, and 
 wherein,
 the composition is in a syringe having two separate compartments, the first aqueous solution is in a first compartment of the two separate compartments, and 
 the second aqueous solution is in a second compartment of the two separate compartments. 
 
 
     
     
       18. The composition according to  claim 17 , wherein the composition further comprises cells, growth factors, or cell nutrients.